Osteoporosis can be classified into postmenopausal osteoporosis, which occurs with an increase in bone resorption caused by activation of osteoclasts due to sudden changes in hormones after menopause, and senile osteoporosis, in which osteogenesis declines due to a decrease in functions of the osteoblasts in elderly men and women. Bone fractures caused by such osteoporosis severely restricts patients' activities. Since hip fractures are associated with a high mortality of approximately 15 to 35%, it is important to diagnose and treat osteoporosis before the onset of osteoporotic bone fractures.
In 2008, it was reported that the prevalence rate of osteoporosis in Korea has increased by approximately 3 times over the last 5 years, and the yearly socioeconomic loss caused by the osteoporosis bone fractures reaches a serious level of approximately 1.05 trillion won. Also, in 2009, the latest Korea Health Statistics show that the prevalence rates of osteoporosis in the total Korean populations over 50 years old and 65 years old are 23.1% and 42.0%, respectively. Among chronic diseases, osteoporosis has immerged as a big issue in national health due to a very high prevalence rate (Korean National Health and Nutrition Examination Survey in 2009).
Therapeutic agents for osteoporosis known in the prior art are bisphosphonate-based drugs. Bisphosphonate is known to deposit into inorganic components of bone, show toxicity to cells with formation of ATP analogues, which are not hydrolyzed when the bone into which bisphosphonate deposits is phagocytized by osteoclasts, or reduce the osteoclast activities in osteoclasts in various manners and cause apoptosis to reduce the bone resorption, thereby causing an increase in bone density. Although such drugs are known to be relatively safe, the drugs have problems in that they may affect the remodeling of bone by normal bone resorption and formation, or bone healing after bone fracture when they are used for a long period of time, and thus cause a decrease in bone elasticity, resulting in an adverse effect on bone strength. In fact, it was reported that stress fractures occur due to the decrease in bone elasticity in many patients.
Therefore, there is an urgent need for finding of a novel bone mechanism associated with the onset of osteoporosis, and prevention of osteoporosis or development of therapeutic agents.
Typically, the bone remodeling (i.e., bone regeneration) has been considered to be mainly regulated by the endocrine system, and locally acting factors such as cytokines, growth factors, etc. However, such a point of view has gradually changed with the evidence that neurological factors can alter the activities of osteocytes. In recent years, much research shows that nerve fibers and neurological factors are found in bone tissues, which supports these facts.
As a sympathetic neurotransmitter, neuropeptide Y (NPY) is a neurotransmitter which is found most abundantly in the brains of mammals, and consists of 36 amino acids. Such a neurotransmitter is known to secrete from a Y2 receptor in the hypothalamus, and play parts in various physiological and pathological conditions such as the control of appetite, memories, and seizure (Balasubramaniam, 1997; Vezzani et al., 1999; Wettstein et al., 1995). In this regard, it was reported that, when our bodies are exposed to stress environments, the secretion of neuropeptide Y from the brain and sympathetic nervous system increases, resulting in obesity due to an increase in phagocytosis. However, there are no research reports known an effect of neuropeptide Y on functional control, release, and homing of bone marrow-derived stem cells such as haematopoietic stem cells, differentiated cells, and immune-related cells, etc. In particular, the relationship between neuropeptide Y andosteoporosis remains to be found.
The present inventors have found that neuropeptide Y may be used to induce the release of haematopoietic stem cells from the bone marrow into blood so as to prevent or treat osteoporosis. Therefore, the present invention has been completed based on these facts.